One of the major problems in development and aging is that we do not understand the nature of the "developmental program" through which a cell passes between birth and death. Insect metamorphosis involves a conspicuous program with many advantages for analysis. We plan to investigate how juvenile hormone blocks progress in the metamorphic program by examining its action on the insect epidermis in tissue culture. We shall establish culture conditions which permit lepidopteran pupal wings to form normal adult cuticles after ecdysone stimulation and pupal cuticles when juvenile hormone is present. We will then determine when pupal and adult cuticular proteins first appear in the cultures, and define the critical period of juvenile hormone's action. Further dissection of the control of the program will involve comparisons of the action of juvenile hormone, inhibitors of transcription and RNA processing, and high levels of ecdysone on the synthesis of specific cuticular proteins. We hope to be able to compare larval wing disks with pupal epidermis and determine the critical levels of hormones needed to direct development. We can then test whether one stage in the program, pupal, can be omitted. Other projects, including some in intact animals, will be directed towards elucidating whether DNA synthesis must occur before reprogramming and whether juvenile hormone's action is related to DNA synthesis. If answers to these two questions are affirmative, then we would determine whether "quantal" mitotic divisions can be recognized by the length of their S-periods. Finally, we hope to investigate whether juvenile hormone's action on cell growth and cell death can be separated from its action in directing macromolecular syntheses.